Biochemical analysis apparatus and incubator for the same

ABSTRACT

In a biochemical analysis apparatus, a dry-type frameless chemical analysis film having a base and a reagent layer formed thereon is taken out from a cartridge in which a plurality of such frameless chemical analysis films are stacked. Then the film is spotted with a sample liquid and is transferred to a cell in an incubator to be incubated at a constant temperature, whereby coloring reaction between the reagent layer and a particular biochemical component in the sample liquid is caused and the optical density of the coloring matter formed is measured. A horseshoe-like film transfer member receives the film taken out from the cartridge and inserts it into the cell while holding it, and a suction member enters the cell from below the cell and holds the film inserted by the film transfer member.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a biochemical analysis apparatus which spots asample liquid such as blood, serum, urine or the like on a dry-typeframeless chemical analysis film having thereon a reagent layer(spreading layer) whose optical density changes by chemical reaction,immunoreaction, or the like with a specific biochemical componentcontained in the sample liquid and determines the concentration of thespecific biochemical component in the sample liquid by measuring theoptical density of the film.

2. Description of the Prior Art

There has been put into practice a biochemical analysis apparatus usinga dry-type chemical analysis film with which a specific componentcontained in a sample liquid can be quantified through a droplet of thesample liquid spotted on the slide. When chemical components or the likecontained in a sample liquid is analyzed using such a dry-type chemicalanalysis film, a droplet of the sample liquid is spotted on the slideand is held at a constant temperature for a predetermined time(incubation) in an incubator so that coloring reaction occurs, and theoptical density of the color formed by the coloring reaction isoptically measured. That is, measuring light containing a wavelengthwhich is pre-selected according to the combination of the component tobe analyzed and the reagent contained in the reagent layer of the filmis projected onto the film and the optical density of the film ismeasured. Then the component to be analyzed is quantified on the basisof the optical density using a calibration curve which represents therelation between the concentration of the biochemical component and theoptical density.

The chemical analysis film is generally composed of a base film ofplastic or the like and a reagent layer and a spreading layer formed onthe base film and is conventionally generally provided with a plasticframe which holds the chemical analysis film flat which is apt to warpinto a roof tile shape when it dries.

The chemical analysis films are transferred to an incubator one by oneafter spotted with a sample liquid. Transfer of the chemical analysisslides can be done, for instance, by a reciprocating claw member asdisclosed in U.S. Pat. Nos. 4,296,069 and 4,568,519 and the like. Theframe facilitates transfer of the chemical analysis film.

However, the frame increases the volume of the chemical analysis filmand results in increase in the size of various parts handling the filmsuch as cells in the incubator for incubating the chemical analysisfilms. Thus the frame of the chemical analysis film is obstructive toreducing the size of the biochemical analysis apparatus and at the sametime reduces the film accommodating capacity of the incubator, whichobstructs increase in handling capability of the overall biochemicalanalysis apparatus.

An attempt to use a dry-type chemical analysis film without frame (willbe referred to as "frameless chemical analysis film", hereinbelow) willencounter the following difficulties. That is, in order to automate theanalysis, the frameless chemical analysis film must be surelytransferred to the incubator and incubated therein. Though the framelesschemical analysis film is apt to warp into a roof tile shape when itdries as described above and the curvature of the warp changes inresponse to spotting of the sample liquid, the sample liquid must beprecisely spotted on the curled frameless chemical analysis film and thefilm must be transferred to the incubator without touching the sampleliquid thereon and the optical density must be measured with the filmheld flat and tightly enclosed.

That is, when the optical density is measured with some films curled andsome films flat, measuring errors are produced. Further increase intemperature during heating differs and progressing rate of coloringreaction varies according to the curvature of the chemical analysisfilm, which can result in measuring errors. Accordingly, measurement ofthe optical density must be effected with the films held flat in theincubator. Further when a part of the film transfer means is in contactwith the sample liquid during transfer of the films spotted with thesample liquid, the sample liquid adhering to the film transfer means cancontaminate the reagent layer on the next chemical analysis film andadversely affect the accuracy of the analysis.

Further when the film transfer means is arranged to hold the film undersuction on the bottom side (the side opposite to the reagent layer) andto insert the film into cell in the incubator, the incubator must beprovided with a passage through which the suction member goes in theincubator, which makes it difficult to seal the film in the cell duringincubation. When the film is not tightly enclosed, the sample liquid canevaporate and the vapor can contaminate other sample liquid, which canadversely affect the accuracy of the analysis.

Further when a transfer mechanism for taking out the chemical analysisslide or the frameless chemical analysis film from a film supplier andtransferring it to the incubator (during the transfer, a sample liquidis spotted on the film or the slide) is provided between the filmsupplier and the incubator to transfer the film or the slide along alinear path, the space between the supplier and the incubator must belarge, which increases the overall size of the chemical analysisapparatus.

SUMMARY OF THE INVENTION

In view of the foregoing observations and description, the primaryobject of the present invention is to provide an biochemical analysisapparatus in which the frameless chemical analysis film can betransferred to an incubator without being contaminated and can beincubated in a tightly enclosed state.

Another object of the present invention is to provide an biochemicalanalysis apparatus in which the space between the film supplier and theincubator can be small and the transfer mechanism for taking out theframeless chemical analysis film from the film supplier and transferringit to the incubator can be compact in size.

Still another object of the present invention is to provide an incubatorwhich is useful to such a biochemical analysis apparatus.

In accordance with one aspect of the present invention, there isprovided a biochemical analysis apparatus in which a dry-type framelesschemical analysis film having a base and a reagent layer formed thereonis taken out from a cartridge in which a plurality of such framelesschemical analysis films are stacked, is spotted with a sample liquid andis transferred to an incubator to be incubated at a constanttemperature, and the concentration of a biochemical component in thesample liquid is measured through a chemical reaction between thereagent layer and the biochemical component, and which is characterizedby having a cell formed in the incubator into which the chemicalanalysis film is inserted, a film transfer means which receives the filmtaken out from the cartridge and holds the film to insert it into thecell, and a holding means which enters the cell from below the cell andholds the film inserted into the cell of the incubator by the filmtransfer means while the film is being held by the film transfer means.

Preferably said film transfer means comprises a film transfer memberwhich is substantially like a horseshoe in shape and attracts theframeless chemical analysis film on the upper surface thereof to hold itunder a suction force, and said holding means comprises a suction memberwhich is moved up and down into and away from the cell through a lightmeasuring window which opens at the bottom of the cell of the incubator.

Further it is preferred that said incubator is provided with a fixingmeans which fixes the frameless chemical analysis film held by theholding means on the bottom of the cell after the film insertion meansis retracted from the cell.

Preferably the fixing means has a film retainer which presses theframeless chemical analysis film against the bottom of the cell only atcorners of the film.

Further it is preferred that the bottom of the cell in the incubator beformed by a substrate which has a flat upper surface and is providedwith a plurality of light measuring windows at predetermined intervals.

In the biochemical analysis apparatus with the arrangement describedabove, the frameless chemical analysis film taken out from the cartridgeis received by the film transfer means with the reagent layer facingupward and the sample liquid is spotted on the reagent layer. Then thefilm 1 spotted with the sample liquid is inserted into the cell in theincubator by the film transfer means and the film transfer meansretracts from the cell after transferring the film to the holding means.Thereafter the holding means sets the film in a predetermined positionin the cell and then retracts from the cell leaving the film there. Inthe cell, the film is incubated in a tightly enclosed state and thecoloring reaction is measured through the light measuring window in thebottom of the cell.

In this manner, the frameless chemical analysis film can be insertedinto the incubator and incubated therein and measurement can be effectedwithout deteriorating the measuring accuracy. Thus in accordance withthe present invention, chemical analysis film without frame can be used,which results in miniaturization of various parts of the biochemicalanalysis apparatus and in reduction of the analyzing cost.

Further when the film transfer means comprises a horseshoe-like filmtransfer member and the holding means comprises a suction member whichis moved up and down into and away from the cell through the lightmeasuring window, the dry-type frameless chemical analysis film can betransferred with a simple structure. Further when the incubator isprovided with a securing means which secures the film on the incubator,incubation of the film can be surely effected. Especially when thesecuring means holds down the film only at the corners thereof, thesample liquid on the film cannot contaminate the securing means. Furtherwhen the bottom of the cell is flat, cleaning of the cell isfacilitated.

In accordance with another aspect of the present invention, there isprovided a biochemical analysis apparatus in which a cartridge forstoring a stack of a plurality of a dry-type frameless chemical analysisfilms each having a base and a reagent layer formed thereon is housed ina film supplier, and the dry-type frameless chemical analysis film istaken out from the cartridge, is spotted with a sample liquid and istransferred to an incubator to be incubated at a constant temperature,and the concentration of a biochemical component in the sample liquid ismeasured through a chemical reaction between the reagent layer and thebiochemical component, wherein the apparatus characterized by having afilm takeout means which takes out the frameless chemical analysis filmfrom the cartridge in the film supplier and conveys the film in a firstdirection and a film transfer means which receives the film from thefilm takeout means and conveys the film in a second direction into theincubator, the first and second directions being at an angle withrespect to each other.

Preferably the first and second directions are at right angles with eachother.

Preferably the sample liquid is spotted on the frameless chemicalanalysis film at the intersection of the first and second directions orin a position near the intersection.

Further preferably the film takeout means is in the form of a suctionmeans and the film transfer means is in the form of a horseshoe-likefilm transfer member.

When the first and second directions are at an angle with each other,i.e., when the first and second directions are not in alignment witheach other, the transfer mechanism including the film takeout means andthe film transfer means need not be in alignment with the film supplierand the incubator, and accordingly, the film supplier and the incubatorcan be positioned close to each other, whereby the chemical analysisapparatus can be small in the overall size.

When the sample liquid is spotted on the frameless chemical analysisfilm at the intersection of the first and second directions or in aposition near the intersection, the mechanism for spotting the sampleliquid on the frameless chemical analysis film can easily positioned notto interfere with the film supplier or the incubator, whereby layout ofthe respective means is facilitated. Further when the film takeout meansis in the form of a suction means and the film insertion means is in theform of a horseshoe-like film transfer member, the direction ofconveyance of the frameless chemical analysis film can be easily changedby a right angle without rotating the film, whereby the film can betransferred from the film takeout means to the film insertion means witha simple structure.

In accordance with still another aspect of the present invention, thereis provided an incubator for incubating at a constant temperature adry-type frameless chemical analysis film which has a base and a reagentlayer formed thereon and has been spotted with a sample liquid and ischaracterized by having a cell into which the frameless chemicalanalysis film can be inserted, a pressing means which presses theinserted frameless chemical analysis film against the bottom of the celland an enclosing means which tightly encloses a space in which theframeless chemical analysis film is accommodated.

Preferably said pressing means presses the frameless chemical analysisfilm at an area where the sample liquid spotted on the film does notspread out. Further it is preferred that said pressing means and theenclosing means be movable relative to each other.

Further it is preferred that said pressing means be formed by a filmretainer which is urged by a first urging means in the direction inwhich the film retainer presses the inserted frameless chemical analysisfilm against the bottom of the cell, and said enclosing means be formedby a cell cover which is urged by a second urging means in the directionin which the cell cover tightly encloses the frameless chemical analysisfilm pressed by the film retainer, at least one of the first and secondurging means being disposed outside the cell cover. The pressing and theenclosing means may be formed integrally with each other and urged by asingle urging means.

In the incubator described above, the frameless chemical analysis filmcan be incubated in a flat state by virtue of the pressing means whichpresses the film against the bottom of the cell and in a tightlyenclosed state by virtue of the enclosing means and the coloringreaction on the film can be measured through, for instance, a lightmeasuring window in the bottom of the cell.

In this manner, the frameless chemical analysis film can be incubated ina flat and tightly enclosed state and measurement can be effectedwithout deteriorating the measuring accuracy. Thus in accordance withthe present invention, chemical analysis film without frame can be used,which results in miniaturization of various parts of the biochemicalanalysis apparatus and in reduction of the analyzing cost.

Further when the pressing means presses the frameless chemical analysisfilm at an area where the sample liquid spotted on the film does notspread out, the pressing means can be prevented from being contaminatedwith the sample liquid. Further when said pressing means and theenclosing means be movable relative to each other, the framelesschemical analysis film can be surely enclosed even if the thickness ofthe film varies. Further when the first and/or second urging means isdisposed outside the cell cover, the inner space of the cell cover canbe smaller in volume and the cell cover has a smaller inner surfacearea, whereby vaporization of the sample liquid can be suppressed andthe concentration of reaction gases can be made constant to stabilizethe reaction, and at the same time the amount of gas to be adsorbed bythe wall of the cell cover can be reduced. Further when the pressingmeans and the enclosing means are formed integrally with each other andurged by a single urging means, the structure is simplified.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view showing a biochemical analysis apparatus inaccordance with an embodiment of the present invention,

FIG. 2 is a perspective view showing spotting of the sample liquid onthe frameless chemical analysis film,

FIG. 3 is a perspective view showing the operation of taking out theframeless chemical analysis film from the cartridge,

FIG. 4 is a front view partly in cross-section of the incubator,

FIG. 5 is an enlarged fragmentary cross-sectional view showing the cellof the incubator,

FIG. 6 is a cross-sectional view taken along line A--A in FIG. 5,

FIG. 7 is a fragmentary cross-sectional view of the incubator as seen inthe radial direction of the incubator,

FIG. 8 is a perspective view showing the film retainer in relation tothe frameless chemical analysis film spotted with the sample liquid,

FIG. 9 is a fragmentary perspective view of the film transfer member,

FIGS. 10A to 10C are schematic views for illustrating procedure fortransferring the film from the suction pad to the film transfer member,

FIGS. 11A to 11G are schematic views for illustrating procedure forinserting the film into the incubator,

FIG. 12 is a view showing the path along which the frameless chemicalanalysis film is transferred to the incubator from the film supplier,

FIG. 13 is a view similar to FIG. 5 but showing a modification of theincubator,

FIG. 14 is a view similar to FIG. 7 but showing the modification of theincubator,

FIG. 15 is a fragmentary cross-sectional view showing anothermodification of the incubator, and

FIG. 16 is a fragmentary cross-sectional view showing still anothermodification of the incubator.

DESCRIPTION OF THE PREFERRED EMBODIMENT

In FIG. 1, a biochemical analysis apparatus 10 in accordance with anembodiment of the present invention comprises a film supplier 11 inwhich a plurality of rectangular dry-type frameless chemical analysisfilms 1 are stored, an incubator 12 which is disposed beside the filmsupplier 11 and incubates the frameless chemical analysis films 1transferred from the film supplier 11, a film transfer means 13 whichtransfers the frameless chemical analysis films 1 from the film supplier11 to the incubator 12, a sample liquid supplier 14 in which a pluralityof sample liquids such as serum, urine or the like are stored, aspotting mechanism 15 which spots one of the sample liquids in thesample liquid supplier 14 on the frameless chemical analysis film 1 onthe way to the incubator 12, and a light measuring system 16 disposedbelow the incubator 12.

As shown in FIG. 2, the frameless chemical analysis film 1 comprises alight-transmissive base film 1a formed of plastic film such aspolyethylene terephthalate and a reagent layer 1b (including a spreadinglayer) formed on the base film 1a. If necessary, a wear-resistantprotective layer of fibrous material such as fabric may be formed on thereagent layer 1b. Such a protective layer may double as the spreadinglayer.

The dry-type frameless chemical analysis film 1 is apt to curl towardthe reagent layer 1b in the dry state before spotting of the sampleliquid, and the curvature varies depending on the dryness and the kindof the reagent layer 1b. The reagent layer 1b contains reagent (chemicalanalysis reagent or immunoassay reagent) which makes coloring reactionwhen it is mixed with a particular component in the sample liquidspotted by a nozzle tip 88 of the spotting mechanism 15 and is incubatedat a constant temperature for a predetermined time. A plurality of kindsof frameless chemical analysis films 1 having different reagent layers1b are prepared according to the terms of analysis, e.g., the chemicalcomponents or solid components to be analyzed in the sample liquids.

The frameless chemical analysis films 1 are stored in cartridges 20(FIG. 3) for the respective terms of analysis. In the cartridge 20, aplurality of the frameless chemical analysis films 1 are stacked withthe base films 1a facing downward. As shown in FIG. 1, the film supplier11 is provided with a plurality of cartridge holding portions 22a whichare arranged in inner and outer circles on a disk-like support 22 and aplurality of cartridges 20 loaded with the frameless chemical analysisfilms 1 are held in the respective cartridge holding portions 22a. Thesupport 22 is supported for rotation on a base portion 24 and is rotatedby a motor not shown so that a predetermined cartridge holding portion22a is brought to a film takeout position where the film transfer means13 takes out a frameless chemical analysis film 1 from the cartridge 20.

The support 22 is provided with a cover 25 which encloses inner space ofthe film supplier 11. The cover 25 is provided with a pair of openings25a provided with lids and the cartridges 20 can be taken out andinserted into the cartridge holding portion 22a through the openings25a. An dehumidifying agent holding portion 27 is formed in the support22 at the center thereof and dehumidifying agent is loaded in thedehumidifying agent holding portion 27 through an opening 25b formed inthe cover 25. The opening 25b is provided with a lid. Thus the innerspace of the film supplier 11 is kept dry.

A film takeout port (not shown) is provided in the lower surface of thecover 25 in the film takeout position and a shutter is provided to openand close the film takeout port. The shutter is opened when theframeless chemical analysis film 1 is taken out from the cartridge 20and a suction pad 70 of the film transfer means 13 is inserted into thefilm supplier 11 through the shutter and takes out the lowermost film 1in the cartridge 20.

The cartridges 20 are loaded in the support 22 so that their filmtakeout openings 20a (FIG. 3) are faced toward the center of the support22 and the film takeout port is elongated in the radial direction of thesupport 22. The suction pad 70 inserted into the film supplier 11through the film takeout port is further inserted into the cartridge 20through an opening in the bottom of the cartridge 20 to attract thelowermost film 1 in the cartridge 20 under a suction force and is movedtoward the center of the support 22 to take out the lowermost film 1from the cartridge 20.

The incubator 12 comprises a disk-like body portion 40 which issupported to be rotated by a drive mechanism 41 disposed below the bodyportion 40 at the center thereof. A plurality of cells 42 are providedin the body portion 40 at predetermined intervals in the circumferentialdirection thereof. The frameless chemical analysis films 1 are incubatedin the cells 42.

As shown in more detail in FIGS. 4 to 8, the body portion 40 comprises alower disk 45 having a flat upper surface and an upper disk 46 providedon the lower disk 45 and is fixed to the lower disk 45 by screws 47. Theperipheral edge portion of the upper disk 46 is bulged upward to form anannular channel open downward. The lower edge of the outer peripheraledge of the upper disk 46 is spaced from the upper surface of the lowerdisk 45 to form an opening 42a which opens in the side surface of theincubator 12 and gives access to the cells 42. A heater 48 is disposedbetween the lower and upper disks 45 and 46 and the disks 45 and 46 areformed of material having high heat conductivity such as aluminum. Theheater 48 is controlled to heat the frameless chemical analysis films 1in the cells 42 to a predetermined temperature (e.g., 37° C.) on thebasis of the output of a temperature sensor 49 (FIG. 5) disposed in thelower disk 45 near the cell 42. The outer surfaces of the lower andupper disks 45 and 46 are coated with thermal insulators 52 and 51.

The body portion 40 is supported by a bearing 50 provided on the lowersurface of the lower disk 45 to be rotatable relative to a base 53. Thelower disk 45 is provided with a central rotary shaft 45a and a gear 54is fixedly mounted on the rotary shaft 45a. The gear 54 is in mesh witha drive gear 56 of a disk drive motor 55, whereby the body portion 40 ofthe incubator 12 is driven by the drive motor 55. A plurality of lightmeasuring windows 59 are formed in the lower disk 45 to be opposed tothe respective cells 42, and a cell cover 64 is provided above each ofthe light measuring windows 59 to tightly enclose the frameless chemicalanalysis film 1 positioned in the cell 42. A film retainer 61 for fixingthe frameless chemical analysis film 1 in a predetermined position isprovided in the cell cover 64. A measuring system 16 has a lightmeasuring head 95 which is disposed below the body portion 40 in a lightmeasuring position, and the body portion 40 is rotated to bring thelight measuring window 59 of one of the cells 42 opposing to the lightmeasuring head 95.

The film retainer 61 has a rectangular frame portion 61a on the lowersurface thereof as shown in FIGS. 6 and 8. The inner dimensions of theframe portion 61a is larger than the outer dimensions of the framelesschemical analysis film 1 and a protrusion 61b is provided at each cornerof the frame portion 61a to project inward. When the film retainer 61 ismoved downward against the film 1, only the protrusions 61b are broughtinto contact with the film 1 so that the retainer 61 is not brought intocontact with the portion S (FIG. 8) over which the sample liquid canspread. The film retainer 61 is urged downward under the force of aspring provided on the upper surface of the retainer 61.

The cell cover 64 has a box-like body portion open downward and ispositioned to surround the film retainer 61. The cell cover 64 is urgeddownward under the force of a spring 65 provided between the top wall ofthe cell cover 64 and the bottom of the channel in the upper disk 46.The lower surface of the cell cover 64 is pressed against the uppersurface of the lower disk 45 to tightly enclose therein the framelesschemical analysis film 1. The spring 62 for urging downward the filmretainer 61 is compressed between the upper surface of the film retainer61 and the top wall of the cell cover 64, and the film retainer 61 isreceived in the cell cover 64 to be slidable relative to the cell cover64 and to be movable up and down together with the cell cover 64.

The cell cover 64 and the film retainer 61 are formed of blackpolyethylene in order to suppress contamination due to adsorption ofgases and influence of internal reflection of small amount of lighttransmitted through the film 1 on the light measurement.

A pair of engaging portions 64a (FIGS. 6 and 7) are formed on diagonallyopposed corners of the lower portion of the cell cover 64 and a pair ofthrough holes 45c are formed in the lower disk 45 to opposed to theengaging portions 64a. A pair of rods 67 are provided in a filminsertion position and in a film takeout position. The rods 67 are movedupward through the holes 45c to abut against the engaging portions 64aof the cell cover 64 and lifts upward the cell cover 64 together withthe film retainer 61 when the frameless chemical analysis film 1 is tobe inserted into the cell 42 or taken out therefrom.

The film transfer means 13 for transferring the frameless chemicalanalysis film 1 from the film supplier 11 to the incubator 12 comprisessaid suction pad 70 which takes out the film 1 from the cartridge 20 andconveys it to a transfer position P in a first direction X (FIG. 12), ahorseshoe-like film transfer member 73 which receives the film 1 held onthe suction pad 70 from below the film 1 with the reagent layer 1bfacing upward in the transfer position and conveys the film 1 in asecond direction of Y perpendicular to the first direction X to insertthe film 1 into the cell 42 in the incubator 12 through the opening 42awhich opens sideways, and a suction member 76 which moves in and out thecell 42 from below the cell and receives the film 1 held by the filmtransfer member 73 inside the cell 42.

As shown in FIG. 3, the suction pad 70 comprises a suction cup 70a whichis directed upward and attracts the lower side of the base film 1a ofthe frameless chemical analysis film 1. The suction cup 70a is supportedon a base portion 70b which is moved back and forth (away and toward thecenter of the support 22) and up and down by a drive mechanism (notshown) and is connected to a suction pump (not shown) through a vacuumtube.

The suction pad 70 is moved upward into the cartridge 20 through anopening in the bottom of the cartridge 20 and attracts the lowermostframeless chemical analysis film 1 on the base film side thereof. Thenthe suction pad 70 is slightly moved downward to curl the lowermost film1 and then horizontally moved toward the center of the support 22 totake out the film 1 from the cartridge through an opening 20a in theside wall of the cartridge with the film 1 held in the curled state.Thereafter the suction pad 70 is moved downward outside the filmsupplier 11 through the film takeout port in the film supplier 11 and ismoved away from the center of the support toward the position where thesample liquid is spotted on the film 1.

As shown in FIG. 9, the film transfer member 73 is like a horseshoe inshape and has a flat upper surface. That is, the film transfer member 73is bifurcated in the front end portion to form a pair of arm portions73b extending on opposite sides of a cutaway portion 73a, and aplurality of suction holes 74 are formed to surround the cutaway portion73a and to open in the upper surface of the film transfer member 73. Thesuction holes 74 are connected to a suction pump (not shown) through avacuum tube 75. The base portion 73c of the film transfer member 73 isconnected to a drive mechanism (not shown) to be inserted into the cell42 in the incubator 12 through the opening 42a.

When the film transfer member 73 receives the film 1 from the suctionpad 70, the film transfer member 73 is moved toward the suction pad 70holding the film 1 as shown in FIG. 10A and is stopped in a positionwhere the suction pad 70 is in the cutaway portion 73a of the filmtransfer member 73 with the film 1 positioned above the cutaway portion73a as shown in FIG. 10B. Then the suction pad 70 is moved downwardbelow the film transfer member 73 leaving the film 1 on the filmtransfer member 73 as shown in FIG. 10C. The film 1 left on the filmtransfer member 73 is held thereon under the suction force providedthrough the suction holes 74. When the position of the suction pad 70relative to the film 1 held thereby is accurately controlled, theposition of the film transfer member 73 relative to the film 1 can beaccurately controlled and a predetermined amount of the sample liquidcan be accurately spotted on the center of the reagent layer 1b of theframeless chemical analysis film 1 held by the film transfer member 73.

As shown in FIG. 5, the suction member 76 is positioned below the cell42 in the incubator 12 and comprises a suction cup 76a supported on abase portion 76b to be moved up and down by a drive mechanism not shown)into and away from the cell 42 through the light measuring window 59.The suction cup 76a is connected to a suction pump (not shown) through avacuum hose.

A film removing means 17 (FIG. 1) is disposed in the film removingposition of the incubator 12. The film removing means 17 comprises aremoving suction pad 81 which attracts the film 1 in the cell 42 whichhas finished with measurement and lifts it, a horseshoe-like filmremoving member 82 which receives the film 1 from the removing suctionpad 81 and transfers it outside the incubator 12 and a discardingsuction pad 83 which receives the film 1 from the film removing member82 and discards it into a discarding box 84.

The sample liquid supplier 14 comprises a turn table 85 which is rotatedby a drive mechanism 86. The turn table 85 holds a plurality of sampletubes 87 filled with sample liquids which are arranged along thecircumferential edge of the turn table 85 and is rotated to bring thesample tubes 87 to a sample liquid supplying position one by one. Aplurality of nozzle tips 88 which are mounted on a spotting nozzle 91 tobe described later are held on the turn table 85 inside the sample tubes87.

The spotting means 15 for spotting the sample liquid on the framelesschemical analysis film 1 to be transferred to the incubator 12 comprisesa spotting nozzle 91 which sucks and discharges the sample liquid, and anozzle tip 88 is demountably mounted on the nozzle 91. The nozzle 91 ismoved up and down and rotated by a drive mechanism 92. That is, thenozzle 91 sucks the sample liquid from the sample liquid supplier 14, ismoved to the film 1 held by the film transfer member 73, and then spotsthe sample liquid on the film 1. The position where the sample liquid isspotted on the film 1 is a point on the path along which the filmtransfer member 73 is moved and is set at the intersection of the firstand second directions X and Y in which the suction pad 70 and the filmtransfer member 73 are moved respectively or close to the intersection.The nozzle tip 88 is changed every time the sample liquid is changed.

The film 1 spotted with the sample liquid is transferred to theincubator 12 and incubated there. After incubation for a predeterminedtime, the optical density of the reagent layer 1b is measured by thelight measuring system 16 (FIG. 1) disposed below the incubator 12. Thelight measuring system 16 comprises said light measuring head 95 formeasuring the optical density of the color formed by the coloringreaction between the reagent layer 1b and the sample liquid. The lightmeasuring head 95 projects measuring light containing light of apredetermined wavelength onto the reagent layer 1b through the base film1a and detects reflected light with a photodetector. Light from a lightsource (lamp) 96 enters the light measuring head 95 through a filter 97and is caused to impinge upon the reagent layer 1b by the head 95. Aplurality of kinds of the filters 97 are mounted on a rotary disk 98which is driven by an electric motor 99 and one of the filters 97 isselected according to the term of measurement.

The reflected light from the reagent layer 1b carries thereon opticalinformation (more particularly the amount of light) on the amount ofcoloring matter formed by the coloring reaction between the reagentlayer 1b and the sample liquid. The reflected light is received by thephotodetector and the optical information carried by the reflected lightis converted to an electric signal by the photodetector. The electricsignal is input into a determination section through an amplifier. Thedetermination section determines the optical density of the coloringmatter formed by the coloring reaction between the reagent layer 1b andthe sample liquid on the basis of the level of the electric signal anddetermines the concentration of a predetermined chemical component inthe sample liquid.

The measurement by the biochemical analysis apparatus 10 is effected inthe following manner. That is, a frameless chemical analysis film 1 istaken out by the suction pad 70 of the film transfer means 13 from acartridge 20 storing therein frameless chemical analysis films 1corresponding to the term of measurement. The film 1 held by the suctionpad 70 is transferred to the film transfer member 73 with the reagentlayer 1b facing upward and a sample liquid is spotted on the reagentlayer 1b.

That is, a nozzle tip 88 is mounted on the spotting nozzle 91 of thespotting means 15 and the spotting nozzle 91 is moved above a desiredsample tube 87 in the sample liquid supplier 14. Then the nozzle 91 ismoved downward to bring the nozzle tip 88 into the sample liquid and thenozzle 91 sucks a predetermined amount of the sample liquid into thenozzle tip 88. Thereafter the nozzle 91 is moved above the center of thefilm 1 on the film transfer member 73 and moved downward toward the film1, where a predetermined amount of sample liquid is spotted on thereagent layer 1b from the nozzle tip 88. The sample liquid spreads overthe reagent layer 1b and mixes with the reagent therein.

The film 1 spotted with the sample liquid is inserted into one of thecells 42 of the incubator 12 through the opening 42a by the filmtransfer member 73. When the film 1 is inserted into the cell 42, theincubator 12 is first rotated to bring a vacant cell 42 to the filminsertion position as shown in FIG. 11A. Then the cell cover 64 islifted together with the film retainer 61 by the rods 67 and the filmtransfer member 73 is inserted into the cell 42 through the opening 42aas shown in FIG. 11B. Then the suction member 76 is moved upward andlifts the film 1 away from the film transfer member 73 as shown in FIG.11C. When the suction member 76 lifts the film 1, it holds the film 1under a suction force. After the film transfer member 73 is retractedaway from the cell 42 as shown in FIG. 11D, the suction member 76 ismoved downward so that the lower side of the film 1 abuts against theupper surface of the lower disk 45 of the incubator 12 as shown in FIG.11E. Then the rods 67 are moved downward to permit the cell cover 64 andthe film retainer 61 to move downward as shown in FIG. 11F. In thisstate, the film 1 is tightly enclosed in the cell cover 64 with the fourcorners thereof held down by the protrusions 61b of the film retainer61. Then the suction member 76 is moved downward as shown in FIG. 11G.

Thus the film 1 is fixed in a predetermined position in the cell 42 andtightly enclosed by the cell cover 64. The light measuring window 59 isclosed by the film 1 itself.

Coloring reaction (coloring matter forming reaction) is caused when thefilm 1 with the sample liquid is heated to a predetermined temperaturein the cell 42 in the incubator 12, and the optical density of thecoloring matter is measured by the light measuring head 95 after apredetermined time or at predetermined intervals.

Referring to FIG. 12, the film 1 taken out from the cartridge 20 by thesuction pad 70 is conveyed radially outwardly of the film supplier 11 inthe first direction X and then transferred to the film transfer member73 in the transfer position P. The film transfer member 73 conveys thefilm 1 toward the center of the incubator 12 in the second direction Yto insert the film 1 into the cell 42. The first and second directions Xand Y are perpendicular to each other and the transfer position P is atthe intersection of the first and second directions X and Y. Thespotting means 15 spots the sample liquid at the transfer point P

When the sample liquid spotted on the film 1 reaches a side of thereagent layer 1b, a part of the sample liquid can overflow and adheresto the side surface of the film 1 though does not drop. If the film 1 isbrought into contact with the film retainer 61 or the like, the sampleliquid will contaminate retainer 61. However, in this embodiment, sincethe film retainer 61 holds down the film 1 only at the four cornersthereof where the sample liquid cannot reach and the other parts of thefilm retainer 61 are spaced from the film 1, the film retainer 61 cannotbe contaminated with the sample liquid.

Further, the film transfer member 73 and suction member 76 are notbrought into contact with the reagent layer 1b of the film 1 duringtransfer of the film 1, they cannot be contaminated with the sampleliquid, whereby accuracy of the measurement can be ensured.

Further in the incubator 12 in the embodiment described above, since themetal disks 45 and 46 are directly heated by the heater 48, the films 1are can be quickly heated and the preheating time can be shortened ascompared with a system in which films 1 are heated on a disk positionedin a temperature-regurated chamber. Further the incubator 12 in theembodiment described above is advantageous over the latter system inthat the chamber is not necessary, the thermal efficiency is high and ashutter for inserting the films 1 into the chamber can be eliminated,whereby the incubator can be simple in structure.

The cell covers 64 are arranged to be fit in the upper disk 46 andaccordingly can be easily removed from the incubator 12 for cleaning orreplacement. Further since the upper disk 46 can be easily removed fromthe incubator 12 by unscrewing the screws 47 and the upper surface ofthe lower disk 45 is flat, the upper surface of the lower disk 45 can beeasily cleaned. Further the space in each cell 42 is closed by the cellcover 64 and the film 1, vapors and gases formed from the film 1 areprevented from flowing outside the cell 42. Since the film retainer 61can be slid up and down, frameless chemical analysis films 1 havingdifferent thicknesses can be surely fixed by the film retainer 61.

Further since the engaging portions 64a of the cell cover 64 are formedon diagonally opposed corners of the lower portion of the cell cover 64,the space between the cell covers 64 can be smaller which results inminiaturization of the system, and at the same time the cell cover 64can be lifted in a balanced position.

By continuing supplying suction force to the removing suction pad 81after it lifts the film 1 and transfers it to the transfer member 82during removal of the film 1 after measurement so that residual gasand/or air in the cell 42 and the vicinity thereof is sucked through thepad 81, the space in the cell 42 can be cleaned.

Though, in the embodiment described above, the present invention isapplied to the biochemical analysis apparatus in which the concentrationof a particular biochemical component is measured the change in theoptical density due to chemical reaction between the particularbiochemical component and the reagent layer, the present invention canbe applied to other biochemical analysis apparatuses such as those inwhich the concentration of an electrolyte is measured through adifference in potential.

Though, in the embodiment described above, the first direction X inwhich the suction pad 70 is moved is directed to the center of the filmsupplier 11 and the second direction Y in which the film transfer member73 is moved is directed to the center of the incubator 12, one or bothof the directions X and Y may be deviated from the center of thecorresponding member. Further, though, in the embodiment describedabove, the first and second directions X and Y are at right angles witheach other, they may be at other angles so long as the film 1 can berotated to conform to the second direction Y when it is transferred fromthe suction pad 70 to the film transfer member 73.

FIG. 13 shows a modification of the incubator 12. Since the modificationis substantially the same as that in the preceding embodiment, the partsanalogous to those described in conjunction with the precedingembodiment are given the same reference numerals and only the differenceof the modification from the incubator 12 in the preceding embodimentwill be described hereinbelow.

As shown in FIG. 13, in this modification, the film retainer 61 has arectangular frame portion 61a on the lower surface thereof. The innerdimensions of the frame portion 61a is larger than the outer dimensionsof the frameless chemical analysis film 1 and a protrusion 61b isprovided at each corner of the frame portion 61a to project inward. Whenthe film retainer 61 is moved downward against the film 1, only theprotrusions 61b are brought into contact with the film 1 so that theretainer 61 is not brought into contact with the portion S (FIG. 8) overwhich the sample liquid can spread. These features are the same as thosedescribed above in conjunction with FIGS. 6 and 8. The film retainer 61has a shank portion 61c extending upward from the top of the retainer61. A spring 62 for urging downward the film retainer 61 is compressedbetween the bottom of the channel in the upper disk 46 and a springretainer 61d provided on the shaft portion 61d.

When the frameless chemical analysis film 1 is arranged so that thesample liquid spotted on the reagent layer 1b spreads laterally as shownin FIG. 8, the protrusions 61b may be arranged to hold down the upperand lower edges of the film 1.

The cell cover 64 has a box-like body portion open downward and ispositioned to surround the film retainer 61. A guide portion 64b isformed in the top wall of the cell cover 64 and the shank portion 61c ofthe film retainer 61 is slidably fitted in the guide portion 64b to beguided by the guide portion 64b in up and down movements of the filmretainer 61 relative to the cell cover 64. The cell cover 64 is receivedin the channel in the upper disk 46 for up and down movements and urgeddownward under the force of a spring 65 provided between the top wall ofthe cell cover 64 and the bottom of the channel in the upper disk 46.When the cell cover 64 is moved upward, the film retainer 61 is movedupward together with the cell cover 64 by way the engagement between thespring retainer 61d and the guide portion 64b as shown in FIG. 14. Inthis modification, since the spring 62 for urging downward the filmretainer 61 is disposed outside the cell cover 64, the inner space ofthe cell cover 64 can be smaller in volume. When the cell cover 64 has asmall inner space, vaporization of the sample liquid can be suppressedand the concentration of reaction gases can be made constant tostabilize the reaction. Further the internal surface area in contactwith the reaction gasses becomes smaller and the amount of gas to beadsorbed by the wall of the cell cover 64 becomes smaller.

FIG. 15 shows another modification of the incubator 12. In thismodification, the film retainer is formed integrally with the cellcover. That is, a cell cover 101 is slidably fitted in the channel ofthe upper disk 46 and is urged downward by a spring 103. The cell cover101 abuts against the upper surface of the lower disk 45 at its lowerend to form a sealed space for accommodating the frameless chemicalanalysis film 1. A film retainer 102 for holding down the four cornersof the film 1 is integrally formed on the inner side of the top wall ofthe cell cover 101. The film retainer 102 is formed of a resilientmaterial to be resiliently pressed against the film 1 when the cellcover 101 is pressed against the lower disk 45 under the force of thespring 103.

FIG. 16 shows still another modification of the incubator 12 where thefilm retainer is formed integrally with the cell cover.

A film retainer 105 similar to that shown in FIG. 13 is provided withprotrusions 105a on the lower surface thereof at the respective cornersto hold down the four corners of the film 1. A shank portion 105bextending upward from the center of the top wall of the film retainer105 is slidably supported by a guide portion 108a formed in a upper disk108. The amount of up and down movement of the film retainer 105 islimited by an abutment portion 105c. The film retainer 105 is urgeddownward under the force of a spring 107. A sealing member 106 formed ofa flexible material extends downward from the film retainer 105 in askirt-like fashion to surround the retainer 105. When the film retainer105 is pressed against the upper surface of the lower disk 45 under theforce of the spring 107, the protrusions 105a of the film retainer 105hold down the film 1 and the lower edge portion of the sealing member106 is pressed against the upper surface of the lower disk 45 to tightlyenclose the film 1.

What is claimed is;
 1. In an incubator comprising means for incubatingat a constant temperature a dry-type frameless chemical analysis filmwhich has a base and a reagent layer formed thereon and has been spottedwith a sample liquid, the improvement comprising;a cell into which theframeless chemical analysis film can be inserted, a pressing means whichpresses the inserted frameless chemical analysis film against the bottomof the cell and an enclosing means which tightly encloses a space withinsaid cell in which the frameless chemical analysis film is accommodated.2. An incubator as defined in claim 1 in which said pressing meanspresses the frameless chemical analysis film at an area where the sampleliquid spotted on the film does not spread out.
 3. An incubator asdefined in claim 1 in which said pressing means and the enclosing meansare movable relative to each other.
 4. An incubator as defined in claim1 in which said pressing means is formed by a film retainer which isurged by a first urging means in the direction in which the filmretainer presses the inserted frameless chemical analysis film againstthe bottom of the cell, and said enclosing means is formed by a cellcover which is urged by a second urging means in the direction in whichthe cell cover tightly encloses the frameless chemical analysis filmpressed by the film retainer, at least one of the first and secondurging means being disposed outside the cell cover.
 5. An incubator asdefined in claim 4 in which the pressing means and the enclosing meansare formed integrally with each other and urged by a single urgingmeans.